Key Laboratory of Cluster Science of Ministry of Education, Beijing Key Laboratory of Photoelectronic/Electrophotonic Conversion Materials, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing, 100081, P. R. China.
J Mater Chem B. 2020 Nov 11;8(43):9943-9950. doi: 10.1039/d0tb00529k.
The current trend of cancer therapy has changed from monotherapy to synergistic or combination therapies. Among the treatment strategies, photodynamic therapy (PDT) and starvation therapy are widely employed together. However, the therapeutic effect of these treatments could lead to strong resistance and poor prognosis due to tumor hypoxia. Therefore, a smart nanoplatform (MONs-GOx@MnO2-Ce6) has been constructed herein by the assembly of glucose oxidase (GOx)-coated mesoporous organosilica nanoparticles (MONs) and MnO2 nanosheets-chlorin e6 (Ce6), which form a nanosystem. Once MONs-GOx@MnO2-Ce6 enter tumor cells, it catalyzes the oxidation of glucose using oxygen (O2) and generates hydrogen peroxide (H2O2) and gluconic acid, the former of which may accelerate the decomposition of MnO2 nanosheets. The released MnO2 nanosheets would regenerate O2 in the presence of H2O2. In this case, MnO2 nanosheets serve as (i) a nanocarrier and fluorescence quencher for the photosensitizer Ce6, (ii) a degradable material that is activated by the tumor microenvironment (TME) for fluorescence recovery, and (iii) an O2-producing carrier that reacts with H2O2 for relieving hypoxia in the tumor, which contributes to the combined starvation/photodynamic cancer therapy since these treatment strategies need O2. MONs-GOx@MnO2-Ce6 could not only realize cancer cell imaging, but also reduce intracellular glucose uptake and Glut1 expression, inhibiting the metabolism of cancer cells. This strategy shows great potential for clinical applications.
当前的癌症治疗趋势已经从单一疗法转变为协同或联合疗法。在这些治疗策略中，光动力疗法（PDT）和饥饿疗法被广泛地联合应用。然而，由于肿瘤缺氧，这些治疗方法的疗效可能会导致强烈的耐药性和较差的预后。因此，本文构建了一种智能纳米平台（MONs-GOx@MnO2-Ce6），通过葡萄糖氧化酶（GOx）包覆的介孔有机硅纳米粒子（MONs）和 MnO2 纳米片-叶绿素 e6（Ce6）的组装形成纳米系统。一旦 MONs-GOx@MnO2-Ce6 进入肿瘤细胞，它就会利用氧气（O2）催化葡萄糖氧化，并生成过氧化氢（H2O2）和葡萄糖酸，前者可能会加速 MnO2 纳米片的分解。在 H2O2 的存在下，释放的 MnO2 纳米片会在原位再生 O2。在这种情况下，MnO2 纳米片充当（i）光敏剂 Ce6 的纳米载体和荧光猝灭剂，（ii）肿瘤微环境（TME）激活的可降解材料，用于荧光恢复，以及（iii）与 H2O2 反应以缓解肿瘤缺氧的 O2 产生载体，这有助于联合饥饿/光动力癌症治疗，因为这些治疗策略需要 O2。MONs-GOx@MnO2-Ce6 不仅可以实现癌细胞成像，还可以减少细胞内葡萄糖摄取和 Glut1 表达，抑制癌细胞的代谢。该策略在临床应用中具有很大的潜力。
